Sub-acute and chronic toxicity study designs MCQs With Answer

Introduction: Sub-acute and chronic toxicity study designs MCQs With Answer is a focused revision resource tailored for M.Pharm students preparing for exams and practical applications in preclinical safety assessment. This blog consolidates key principles of repeated-dose toxicity testing — covering study durations (sub-acute, sub-chronic, chronic), regulatory guidelines (OECD/ICH), study design elements (dose selection, group size, sexes, routes), critical endpoints (clinical signs, hematology, biochemistry, organ weights, histopathology), recovery/satellite groups and toxicokinetics. The multiple-choice questions target conceptual understanding and regulatory practice to strengthen decision-making skills when planning, executing or interpreting sub-acute and chronic toxicity studies in a GLP environment.

Q1. What is the commonly accepted duration for a sub-acute (repeated dose) toxicity study?

• 14 days
• 28 days
• 90 days
• 6 months

Correct Answer: 28 days

Q2. Which OECD test guideline describes the 28‑day repeated dose toxicity study?

• OECD TG 408
• OECD TG 452
• OECD TG 407
• OECD TG 453

Correct Answer: OECD TG 407

Q3. Which guideline is most appropriate for a 90‑day sub‑chronic toxicity study in rodents?

• OECD TG 407
• OECD TG 408
• OECD TG 452
• OECD TG 440

Correct Answer: OECD TG 408

Q4. Which OECD guideline is designated for chronic toxicity studies?

• OECD TG 407
• OECD TG 408
• OECD TG 452
• OECD TG 451

Correct Answer: OECD TG 452

Q5. Which guideline covers combined chronic toxicity and carcinogenicity studies?

• OECD TG 408
• OECD TG 453
• OECD TG 407
• OECD TG 414

Correct Answer: OECD TG 453

Q6. What is the typical recommended group size per sex per dose in a 90‑day rodent toxicity study?

• 3 animals per sex per dose
• 10 animals per sex per dose
• 30 animals per sex per dose
• 50 animals per sex per dose

Correct Answer: 10 animals per sex per dose

Q7. What is the main purpose of including a recovery (satellite) group in sub‑acute and chronic studies?

• To increase statistical power for primary endpoints
• To evaluate reversibility, persistence or delayed occurrence of toxic effects
• To reduce the number of dose levels needed
• To serve as additional controls for histopathology only

Correct Answer: To evaluate reversibility, persistence or delayed occurrence of toxic effects

Q8. Which regulatory metric is most commonly used to select a safe starting dose for first‑in‑human clinical trials?

• LOAEL (Lowest Observed Adverse Effect Level)
• NOAEL (No Observed Adverse Effect Level)
• ED50 (Median Effective Dose)
• LD50 (Median Lethal Dose)

Correct Answer: NOAEL (No Observed Adverse Effect Level)

Q9. LOAEL is best defined as which of the following?

• The highest dose with no treatment‑related effects
• The lowest dose that produces a statistically significant beneficial effect
• The lowest dose that produces an observed adverse effect
• The dose that causes death in 50% of animals

Correct Answer: The lowest dose that produces an observed adverse effect

Q10. How is Maximum Tolerated Dose (MTD) defined in repeated‑dose toxicity studies?

• The dose that causes no observable effects
• The highest dose that produces minimal but non‑lethal toxic effects without undue suffering
• The dose that results in 50% mortality
• The lowest dose producing any biochemical change

Correct Answer: The highest dose that produces minimal but non‑lethal toxic effects without undue suffering

Q11. Which of the following endpoints is specifically emphasized in chronic toxicity studies (and may require separate carcinogenicity evaluation) compared with sub‑acute studies?

• Clinical observations
• Short‑term hematology
• Carcinogenic potential and late‑onset neoplastic lesions
• Body weight monitoring

Correct Answer: Carcinogenic potential and late‑onset neoplastic lesions

Q12. Why is toxicokinetic (TK) sampling commonly incorporated into repeated‑dose toxicity studies?

• To replace histopathology evaluations
• To relate systemic exposure and internal dose to observed toxic effects
• To determine food consumption patterns
• To measure organ weight changes directly

Correct Answer: To relate systemic exposure and internal dose to observed toxic effects

Q13. Which assessment is NOT typically a routine part of sub‑acute and chronic toxicity studies and usually requires a dedicated study?

• Hematology and clinical chemistry
• Gross necropsy and histopathology
• Embryo‑fetal development / teratogenicity evaluation
• Urinalysis

Correct Answer: Embryo‑fetal development / teratogenicity evaluation

Q14. For nonclinical toxicity studies intended for regulatory submission, which quality system is expected to be followed?

• ISO 9001 only
• Good Laboratory Practice (GLP)
• Good Clinical Practice (GCP)
• No formal quality system required

Correct Answer: Good Laboratory Practice (GLP)

Q15. Which statistical approach is most appropriate for comparing continuous endpoints across multiple dose groups in a toxicity study?

• Student’s t‑test for each pair
• Analysis of variance (ANOVA) followed by post‑hoc comparisons
• Kruskal–Wallis for binary data only
• Fisher’s exact test

Correct Answer: Analysis of variance (ANOVA) followed by post‑hoc comparisons

Q16. Why should both sexes typically be included in sub‑acute and chronic toxicity studies?

• To double the sample size for better statistics
• Because males are always more sensitive than females
• To detect sex‑related differences in toxicity, pharmacokinetics and target organs
• To follow animal facility traditions

Correct Answer: To detect sex‑related differences in toxicity, pharmacokinetics and target organs

Q17. How are histopathological lesion severities conventionally graded in repeated‑dose studies?

• Present or absent only
• Minimal, mild, moderate and severe
• Positive or negative
• Numerical grades from 0 to 100

Correct Answer: Minimal, mild, moderate and severe

Q18. Satellite groups in chronic studies are often reserved for which uses?

• Extra controls for randomization only
• Toxicokinetic profiling and recovery/reversibility assessments
• Replacing the main study animals halfway through
• Only for breeding and colony maintenance

Correct Answer: Toxicokinetic profiling and recovery/reversibility assessments

Q19. When selecting the route of administration for a repeated‑dose toxicity study, which principle should guide the choice?

• Use the easiest route for dosing animals
• Always use intravenous dosing regardless of clinical route
• Prefer the route intended for human clinical use or a relevant route of exposure
• Use the route that produces the highest systemic exposure only

Correct Answer: Prefer the route intended for human clinical use or a relevant route of exposure

Q20. What is the difference between NOEL and NOAEL?

• NOEL denotes no observed effect level; NOAEL denotes no observed adverse effect level
• NOEL is always higher than NOAEL
• NOAEL is used only in acute studies while NOEL is for chronic studies
• They are interchangeable terms with identical meanings

Correct Answer: NOEL denotes no observed effect level; NOAEL denotes no observed adverse effect level

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